Remission induction therapies and long-term outcomes in granulomatosis with polyangiitis and microscopic polyangiitis: real-world data from a European cohort.

To explore disease characteristics, renal involvement and induction treatment strategies over the last decades and evaluate relapse rates and renal outcomes in ANCA-associated vasculitides (AAV). We retrospectively analyzed remission, relapse rates and the occurrence of the composite endpoint (comprising death and renal failure) in newly diagnosed AAV cases in four tertial referral centers in Germany and Switzerland diagnosed between 1999 and 2022. Hazard ratios were computed by Cox proportional hazard and Kaplan-Meier curves were plotted to compare therapeutic strategies after propensity-matching.

Infiltrative classical monocyte-derived and SPP1 lipid-associated macrophages mediate inflammation and fibrosis in ANCA-associated glomerulonephritis.

Background And Hypothesis: Kidney macrophage infiltration is a histological hallmark of vasculitic lesions and is strongly linked to disease activity in anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AGN). The precise mechanisms by which kidney macrophages influence local inflammation and long-term damage remain largely unknown.

Methods: Here, we investigate kidney macrophage diversity using single-cell transcriptome analysis of 25 485 freshly retrieved unfrozen, high-quality kidney CD45+ immune cells from five AGN patients during active disease, a lupus nephritis and nephrectomy control.

Social Risk Factors Associated With Microbial Keratitis.

Purpose: The objective of this study was to identify social risk factors (SRFs) that affect microbial keratitis (MK) care using the Penchansky-Thomas (P-T) health care access framework.

Methods: This combined retrospective and prospective cohort study recruited participants with newly diagnosed MK at an academic medical center. Participant demographic information and SRFs were collected using in-person interviews and chart review.

Evidence-based guideline: premature ovarian insufficiency.

Study Question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed based on the best available evidence from published literature?

Summary Answer: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI.

What Is Known Already: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular, and cognitive health.

Evidence-based guideline: Premature Ovarian Insufficiency.

Study Question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature?

Summary Answer: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI.

What Is Known Already: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular and cognitive health.

Suppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.

Huntington's disease (HD) arises from a CAG expansion in the () gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant mRNA (m) and protein (mHTT) with the aim of reducing the toxicity of these product(s). Human genetic data also support a key role for somatic instability (SI) in 's CAG repeat - whereby it lengthens with age in specific somatic cell types - as a key driver of age of motor dysfunction onset.

Procollagen-lysine 2-oxoglutarate 5-dioxygenases are responsible for 5R-hydroxylysine modification of therapeutic T-cell bispecific monoclonal antibodies produced by Chinese hamster ovary cells.

We present a detailed mass spectrometric analysis of three 2 + 1 T-cell bispecific monoclonal antibodies (TCB mAbs), where an unexpected +15.9950 Da mass shift in tryptic peptides was observed. This modification was attributed to the occurrence of 5R-hydroxylysine (Hyl) using a hybrid LC-MS/MS molecular characterization and CRISPR/Cas9 gene deletion approach.

Don't forget the dams! Dairy cows' responses to two separation methods after 3 months of cow-calf contact.

Weaning and separation remain among some of the biggest challenges for cow-calf contact systems, making the development of practical and low stress separation methods mandatory for future success of these systems. This study aimed to compare behavioral and physiological responses of dairy cows to separation from their calves after 3 mo of full-time contact with either the 2-step method (NF, 2 wks full-time contact while calves wore a nose flap, 1 wk fence-line contact before total separation, n = 18) or by gradual reduction of contact time between cow and calf (GR, 1 wk half day contact, 1 wk morning contact, 1 wk fence-line contact before total separation, n = 18). Vocalizations and searching behavior were observed on 4 d/wk from 1 wk before separation until 1 wk after total separation.

Substrate specificity and kinetic mechanism of 3β-hydroxy-Δ-C-steroid oxidoreductase.

Cholesterol is a key sterol whose homeostasis is primarily maintained through bile acid metabolism. Proper bile acid formation is vital for nutrient and fat-soluble vitamin absorption and emulsification of lipids. Synthesis of bile acids occurs through two main pathways, both of which rely on 3β-hydroxy-Δ-C-steroid oxidoreductase (HSD3B7) to begin epimerization of the 3β hydroxyl of cholesterol into its active 3α conformation.

Perivascular space enlargement accelerates in ageing and Alzheimer's disease pathology: evidence from a three-year longitudinal multicentre study.

Background: Perivascular space (PVS) enlargement in ageing and Alzheimer's disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD.

Methods: We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; mean = 70.

Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine.

Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP).

Equilibrium Structures of Propane and 2,2-Difluoropropane and Comparison with Other Two-Top Molecules.

The Born-Oppenheimer ab initio equilibrium structures of propane (CH)CH and 2,2-difluoropropane (CH)CF were computed at the CCSD(T) level of theory using a basis set of quadruple zeta quality. The semiexperimental structure of propane was also determined from the ground state rotational constants corrected for rovibrational corrections calculated at the MP2 level of theory. Structural comparisons are made with other molecules and are discussed in terms of the quantum theory of atoms in molecules.

Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study.

Severe acute ischemic stroke (AIS) is mainly caused by thromboembolism originating from symptomatic carotid artery (ICA) stenosis or in the heart due to atrial fibrillation. Glycoprotein VI (GPVI), a principal platelet receptor, facilitates platelet adherence and thrombus formation at sites of vascular injury such as symptomatic ICA stenosis. The shedding of GPVI from the platelet surface releases soluble GPVI (sGPVI) into the circulation.

Perioperative Detection of Cerebral Fat Emboli From Bone Using High-Frequency Doppler Ultrasound.

Objective: Fat embolism syndrome and cerebral fat emboli are rare yet serious conditions arising from systemic distribution of bone marrow emboli. Emboli are known to produce high-intensity transient signals (HITS) in a Doppler signal. We hypothesized that both intramedullary nailing in pigs and median sternotomy in human infants cause bone marrow release, that some of these cause cerebral emboli, and that these were detectable by a new cerebral doppler ultrasound monitoring system (NeoDoppler).

Neural correlates of systemic lidocaine administration in healthy adults measured by functional MRI: a single arm open label study.

Introduction: Intravenous lidocaine is increasingly used as a nonopioid analgesic, but how it acts in the brain is incompletely understood. We conducted a functional MRI study of pain response, resting connectivity, and cognitive task performance in volunteers to elucidate the effects of lidocaine at the brain-systems level.

Methods: We enrolled 27 adults (age 22-55 yr) in this single-arm, open-label study.

Large Language Models for Simplified Interventional Radiology Reports: A Comparative Analysis.

Purpose: To quantitatively and qualitatively evaluate and compare the performance of leading large language models (LLMs), including proprietary models (GPT-4, GPT-3.5 Turbo, Claude-3-Opus, and Gemini Ultra) and open-source models (Mistral-7b and Mistral-8×7b), in simplifying 109 interventional radiology reports.

Methods: Qualitative performance was assessed using a five-point Likert scale for accuracy, completeness, clarity, clinical relevance, naturalness, and error rates, including trust-breaking and post-therapy misconduct errors.

The differential impact of early graft dysfunction in kidney donation after brain death and after circulatory death: Insights from the Dutch National Transplant Registry.

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes.

Efficacy of spp. and sp. Both Independently and Combined with Fungicides against on Strawberries.

The ascomycete is a major pathogen of strawberry, often causing grey mold and significant yield losses. Its management has largely relied on chemical fungicides, which, while effective, can lead to resistant pathogens and harm to non-target organisms and pose health risks. This study explored a strategy for minimizing chemical usage by combining biocontrol agents (BCAs) with half-strength fungicide input.

Human Alzheimer's Disease ATN/ABC Staging Applied to Aging Rhesus Macaque Brains: Association With Cognition and MRI-Based Regional Gray Matter Volume.

The brain changes of Alzheimer's disease (AD) include Abeta (Aβ) amyloid plaques ("A"), abnormally phosphorylated tau tangles ("T"), and neurodegeneration ("N"). These have been used to construct in vivo and postmortem diagnostic and staging classifications for evaluating the spectrum of AD in the "ATN" and "ABC" ("B" for Braak tau stage, "C" for Consortium to Establish a Registry for Alzheimer's Disease [CERAD] neuritic plaque density) systems. Another common AD feature involves cerebral amyloid angiopathy (CAA).

Convergences and Divergences in the Burden of Disease in Older People Across The Organisation for Economic Cooperation and Development Countries.

Background: The Organization for Economic Cooperation and Development (OECD) member states are heterogeneous in their social, economic, and health conditions.

Aims: a) to analyze age-specific mortality rate (ASMR) and age-specific disability-adjusted life year (DALY) rate among older people in countries by age groups (65-74 years and 75+ years) and sex, and b) to estimate the association between age-specific DALY rate with Socio-Demographic Index (SDI) and with Healthcare Access and Quality Index (HAQI).

Methods: Secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

Fast, Easy, and Reproducible Fingerprint Methods for Endotoxin Characterization in Nanocellulose and Alginate-Based Hydrogel Scaffolds.

Nanocellulose- and alginate-based hydrogels have been suggested as potential wound-healing materials, but their utilization is limited by the Food and Drug Administration (FDA) requirements regarding endotoxin levels. Cytotoxicity and the presence of endotoxin were assessed after gel sterilization using an autoclave and UV treatment. A new fingerprinting method was developed to characterize the compounds detected in cellulose nanocrystal (CNC)- and cellulose-nanofiber (CNF)-based hydrogels using both positive- and negative-ion mode electrospray ionization Fourier transform ion cyclotron resonance mass spectroscopy (ESI FT-ICR MS).

Recruitment and retention of pediatric participants for pandemic preparedness research: Experience from the PREMISE EV-D68 Pilot Study.

Recruitment and retention are challenges for prospective pediatric cohort studies, particularly those involving serial venipunctures. We investigated factors underlying enrollment and retention in the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) Enterovirus D68 (EV-D68) Pilot Study, a multicenter prospective longitudinal cohort study assessing the utility of immunologic surveillance for pandemic preparedness. This study enrolls children ≤10 years for two blood draws, pre- and post-EV-D68 season, separated by 6-18 months.

Genetic Variance in Heparan Sulfation Is Associated With Salt Sensitivity.

Background: High heritability of salt sensitivity suggests an essential role for genetics in the relationship between sodium intake and blood pressure (BP). The role of glycosaminoglycan genes, which are crucial for salinity tolerance, remains to be elucidated.

Methods: Interactions between 54 126 variants in 130 glycosaminoglycan genes and daily sodium excretion on BP were explored in 20 420 EPIC-Norfolk (European Prospective Investigation Into Cancer in Norfolk) subjects.